Midfacial growth and dental arch relationships in bilateral cleft palate following secondary alveolar bone grafting and orthodontic intervention: Factors predicting a Le Fort I osteotomy at age 18

Objective

To evaluate midfacial growth and dental arch relationships in patients treated for bilateral cleft lip and palate (BCLP).

Macrophage colony formation supported by purified CSF-1 and/or interleukin 3 in serum-free culture: evidence for hierarchical difference in macrophage colony-forming cells

Using a serum-free culture system, we examined murine macrophage colony formation from bone marrow cells cultured in the presence of purified CSF-1, interleukin 3 (IL 3) or a combination of the two factors. CSF-1 supported macrophage and neutrophil-macrophage colony formation, whereas IL-3 supported the formation of various types of single lineage and multilineage colonies. CSF-1 supported more macrophage colonies from bone marrow cells of normal mice than IL 3, whereas in cultures of bone marrow cells of 5-fluorouracil-treated mice, IL 3 supported more macrophage colonies. A combination of CSF-1 and IL 3 resulted in granulocyte-macrophage (GM) colony formation that was equal to or greater than the sum of GM colony formation supported by the factors individually. The combination of CSF-1 and IL 3 resulted in significant increases in the size of both macrophage and neutrophil-macrophage colonies. Similar increases in colony size were observed when CSF-1 was added to cultures five days after incubation of marrow cells with IL 3. These data support the concept that some of the macrophage colony- forming cells that respond to IL 3 are more primitive than those that are sensitive to CSF-1.     

Dentistry and criminal law

Criminal law in dentistry, as shaped and moulded by the prevailing views of society, defines what is or is not socially acceptable. It applies in both personal and professional contexts with the intended consequence of protecting the public from unacceptable conduct and potential imbalances of power. At its centre, a patient's consent plays a pivotal role in transforming unlawful conduct into lawful conduct. This literature review considers the current law and the trend of utilizing criminal law in addition to non‐criminal law alternatives of reprimanding clinicians for failure to achieve consent in the course of dental practice. Dentists must appreciate this change and the prosecuting authority's increasing willingness to resort to criminal law.     

Induction of tyrosine phosphorylation of Vav and expression of Pim-1 correlates with Jak2-mediated growth signaling from the erythropoietin receptor

The receptor for erythropoietin (Epo) belongs to the cytokine receptor family and lacks a tyrosine kinase domain. However, it has been hypothesized that a tyrosine kinase, Jak2, associates with the membrane proximal cytoplasmic region of Epo receptor (EpoR) and mediates the growth signaling from the receptor through tyrosine phosphorylation of cellular substrates. To explore the growth signaling pathways from the EpoR, we analyzed substrates of tyrosine phosphorylation induced by Epo stimulation in cells expressing various mutant EpoRs. The vav proto- oncogene product was found to be tyrosine phosphorylated after Epo stimulation in cells expressing the wild-type EpoR or a truncated receptor, H mutant, that retains the growth signaling function. In these cells, Epo also induced the expression of a serine/threonine kinase, Pim-1. However, Epo stimulation did not have any effect on Vav or Pim-1 in cells expressing a mutant EpoR, PM4 mutant, inactivated by a point mutation, Trp282 to Arg, in the membrane proximal region, which abrogates the interaction with Jak2. On the other hand, both tyrosine phosphorylation of Vav and expression of Pim-1 were observed constitutively in cells expressing a mutant EpoR that is constitutively activated by a point mutation, Arg 129 to Cys, in the extracellular domain. Jak2 was also constitutively tyrosine phosphorylated and activated in cells expressing this mutant, which confirms the crucial role of Jak2 in growth signaling from the EpoR. Taken together, these observations suggest that the tyrosine phosphorylation of Vav and the expression of Pim-1 may play important roles in growth signaling from the EpoR.     

Suppression of fever and the acute-phase response in a patient with juvenile chronic arthritis treated with monoclonal antibody to tumour necrosis factor-alpha (cA2)

Juvenile chronic arthritis (JCA) is the commonest chronic rheumatic disorder of childhood. Although conventional therapy of JCA continues to improve, many patients experience long-term ill health as a result of their disease or treatment. In adult rheumatoid arthritis (RA), similar concerns have led to the development of therapies designed to interfere in key disease processes. One such therapy is cA2, a chimeric neutralizing monoclonal antibody to the inflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha). The administration of cA2 in adult RA has led to impressive short-term suppression of disease, with a good safety profile. Here, we report the first use of cA2 in childhood arthritis, choosing a patient with severe systemic-onset JCA, resistant to conventional therapies. The patient received two i.v. infusions of cA2, each at a dose of 10 mg/kg, separated by 1 week. The treatment was well tolerated and induced rapid control of fever, anorexia and serositis, together with downregulation of interleukin (IL)-6, soluble TNF receptors (sTNFR) and IL-1ra, and the acute-phase proteins C- reactive protein (CRP) and serum amyloid A (SAA). In contrast, we saw no significant improvement in joint pain or tenderness. Our findings suggest that TNF-alpha is a mediator of fever and other systemic aspects of disease in systemic JCA. TNF-alpha blockade as a treatment modality in JCA deserves further study.